PUBLICATION

Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation

Authors

Hochgreb-Hägele, T., Koo, D.E., Bronner, M.E.

ID

ZDB-PUB-150201-4

Date

2015

Source

Developmental Biology 400(1): 23-32 (Journal)

Registered Authors

Bronner-Fraser, Marianne

Keywords

Cartilage maturation, Neural crest, Ossification, Zebrafish, p53

MeSH Terms

DNA-Binding Proteins/metabolism*
Alcian Blue
Blotting, Western
In Situ Hybridization
Chromatin Immunoprecipitation
Anthraquinones
Osteogenesis/physiology*
Jaw/embryology*
Jaw/metabolism
Gene Expression Regulation, Developmental/physiology*
Cloning, Molecular
Molecular Sequence Data
Gene Expression Profiling
Chondrocytes/metabolism
Alternative Splicing/physiology
Tumor Suppressor Protein p53/metabolism*
Animals
Time Factors
Zebrafish Proteins/metabolism*
Cyclin-Dependent Kinase Inhibitor p21/metabolism*
Amino Acid Sequence
Models, Biological
Microscopy, Fluorescence
Zebrafish/embryology*
Binding Sites/genetics

(all 25)

PubMed

25636963 Full text @ Dev. Biol.

Abstract

Jaw formation involves an intricate series of molecular events, whereby a chondrogenic scaffold precedes osteogenesis. The mechanisms coupling timing of cartilage maturation to onset of bone differentiation are poorly understood, particularly for neural crest-derived bones of the head. Here we present a novel zebrafish gene/protein-trap Citrine-fusion line that reveals transient expression of the zinc-finger protein Znf385C in maturing chondrocytes of the jaw. Functional analysis shows that loss of Znf385C disrupts a distinct peak of p21(cip1/waf1) expression in the chondrocytes, as well as causes premature ossification of the zebrafish jaw. We find that Znf385C is expressed as two splice variants which act differentially to activate p21(cip1/waf1) and/or interact with p53 in subcellular compartments. Taken together, the results suggest that Znf385C acts as a developmental switch for p53 function that modulates cell cycle arrest of chondrocytes and regulates timing of jaw cartilage maturation and ossification.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bbc3	WT	standard conditions	Long-pec to Days 7-13	mandibular arch skeleton	RTPCR	Fig. 4
bcl2l1	WT	standard conditions	Long-pec to Days 7-13	mandibular arch skeleton	RTPCR	Fig. 4
cdkn1a	WT	control	Protruding-mouth to Days 7-13	mandibular arch skeleton	RTPCR	Fig. 4
cdkn1a	WT	standard conditions	Long-pec to Days 7-13	mandibular arch skeleton	RTPCR	Fig. 4
cdkn1a	WT + MO1-znf385c	standard conditions	Protruding-mouth to Days 7-13	mandibular arch skeleton	RTPCR	Fig. 4
Citrine	znf385c^ct39aGt	standard conditions	Day 4	central nervous system neuron	IFL	Fig. 1
Citrine	znf385c^ct39aGt	standard conditions	Long-pec	hindbrain	ISH	Fig. 1
Citrine	znf385c^ct39aGt	standard conditions	Protruding-mouth	inner ear chondrocyte	IFL	Fig. 1
Citrine	znf385c^ct39aGt	standard conditions	Protruding-mouth	mandibular arch skeleton chondrocyte	IFL	Fig. 1
Citrine	znf385c^ct39aGt	standard conditions	Protruding-mouth	pectoral fin chondrocyte	IFL	Fig. 1

1 - 10 of 22

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-znf385c	standard conditions	Long-pec	forebrain apoptotic, abnormal	Fig. 3
WT + MO1-znf385c	standard conditions	Long-pec	head decreased size, abnormal	Fig. 2
WT + MO1-znf385c	standard conditions	Long-pec	heart apoptotic, abnormal	Fig. 3
WT + MO1-znf385c	standard conditions	Long-pec	heart edematous, abnormal	Fig. 2
WT + MO1-znf385c	standard conditions	Long-pec	hindbrain apoptotic, abnormal	Fig. 3
WT + MO1-znf385c	standard conditions	Long-pec	mandibular arch skeleton atrophied, abnormal	Fig. 2
WT + MO1-znf385c	standard conditions	Long-pec	pharyngeal arch apoptotic, abnormal	Fig. 3
WT + MO1-znf385c	standard conditions	Day 4	ceratohyal cartilage decreased size, abnormal	Fig. 2
WT + MO1-znf385c	standard conditions	Day 4	Meckel's cartilage decreased width, abnormal	Fig. 2
WT + MO1-znf385c	standard conditions	Day 6	Meckel's cartilage endochondral ossification premature, abnormal	Fig. 2

1 - 10 of 16

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ba2Tg	Tg(-4.9sox10:EGFP)	Transgenic Insertion
ct39aGt	Gt(FRT-LOXP-Citrine-LOX2272-mCherry-LOXP-LOX2272-FRT)	Transgenic Insertion	znf385c

1 - 2 of 2

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
znf385c	MO1-znf385c	MRPHLNO

Fish

Fish
ba2Tg
ba2Tg + MO1-znf385c
WT
WT + MO1-znf385c
znf385c^ct39aGt

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab12-tp53	polyclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
Citrine	EFG	Citrine
EGFP	EFG	EGFP

Mapping

Hochgreb-Hägele et al., 2015 ZDB-PUB-150201-4 PMID:25636963

Znf385C mediates a novel p53-dependent transcriptional switch to control timing of facial bone formation

Hochgreb-Hägele et al., 2015

ZDB-PUB-150201-4
PMID:25636963